64 articles - From Saturday Apr 30 2022 to Friday May 06 2022
Guidelines, position statements, white papers, technical reviews, consensus statements, etc…
| Ann Oncol |
| Blood Adv |
American Society of Hematology living guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19: January 2022 update on the use of therapeutic-intensity anticoagulation in acutely ill patients. This conditional recommendation was based on very low certainty in the evidence, underscoring the need for additional, high-quality, randomized controlled trials comparing different intensities of anticoagulation in patients with COVID-19-related acute illness. |
meta-analyses and systematic reviews
RCT, clinical trials, retrospective studies, etc…
| Am J Hematol |
A Novel Adoptive Synthetic TCR and Antigen Receptor (STAR) T-Cell Therapy for B-Cell Acute Lymphoblastic Leukemia. Our preclinical studies demonstrate super anti-tumor potency of STAR-OX40 T-cells compared to conventional CAR-T cells. The first-in-human clinical trial shows that STAR-OX40 T cells are tolerable and an effective therapeutic platform for treating R/R B-ALL. |
CAR-T cell therapy targeting B cell maturation antigen is effective for relapsed/refractory multiple myeloma, including cases with poor performance status. OS was not reached in ECOG 0-2 patients, but was 10.5 months (95% CI 0-22) in ECOG 3-4 patients. Single-cell sequencing indicated that treatment efficacy might be related to mTORC1 signaling. Thus, HDS269B therapy is safe and effective for RRMM patients, even those with ECOG 3-4. |
| Ann Oncol |
| Blood |
Anti-CCR9 Chimeric Antigen Receptor T cells for T Cell Acute Lymphoblastic Leukemia. Here, we demonstrate that the chemokine receptor CCR9 is expressed in >70% of cases of T-ALL, including >85% or relapsed/ refractory disease, and only on a small fraction (<5%) of normal T cells. Using cell line models and patient-derived xenografts, we show chimeric antigen receptor (CAR)-T cells targeting CCR9 are resistant to fratricide and have potent anti-leukemic activity both in vitro and in vivo, even at low target antigen density. We propose anti-CCR9 CAR-T cells could be a highly effective treatment strategy for T-ALL, avoiding T cell aplasia and the need for genome engineering that complicate other approaches. |
Approval of brexucabtagene autoleucel for adults with relapsed and refractory acute lymphocytic leukemia. In October 2021, brexucabtagene autoleucel became the first anti-CD19 chimeric antigen receptor T cell product to receive approval from the US Food and Drug Administration to treat adults with relapsed and refractory B cell acute lymphoblastic leukemia (r/r ALL). The approval is based on results from the Zuma-3 trial and significantly widens treatment options for this patient population. In this article we will review outcomes from this study and its implications. |
Bortezomib and high-dose melphalan conditioning regimen in frontline multiple myeloma: an IFM randomized phase 3 study. The proportion of grade 3/4 AEs was similar within the 2 groups (72.0% vs 73.1%), mainly (as expected) blood and gastrointestinal disorders; 4% of patients reported grade 3/4 or painful peripheral neuropathy in arm A (vs 1.5% in arm B). In this randomized phase 3 study, a conditioning regimen with Bor-HDM did not improve efficacy end points or outcomes compared with HDM alone. The original trial was registered at as #NCT02197221. |
Characterization of metabolic alterations of Chronic Lymphocytic Leukemia in the lymph node microenvironment. Finally, inhibition of glutamine import with V9302 attenuated CD40/BCR-induced resistance to venetoclax. Altogether, these data provide insight into crucial metabolic changes driven by CLL LN microenvironment. The prominent use of amino acids as fuel for the TCA cycle suggests new therapeutic vulnerabilities. |
Daratumumab in amyloidosis. Daratumumab based regimes achieve deep hematologic and organ responses; offering a new therapeutic backbone. Early identification, correct fibril typing, challenges of the very advanced patient and lack of therapies to remove amyloid deposits remains under study but as yet elusive. We review the progress of treatment in AL amyloidosis, the impact of daratumumab and look towards the next steps. |
Expansion of CD4dimCD8+T cells characterizes macrophage activation syndrome and other secondary HLH. These findings were confirmed in a prospective replication cohort, in which no expansion of particular TCR Vß family in CD3+ T cells of sHLH patients was found. Finally, frequency of CD4dimCD8+, but not of CD38high/HLA-DR+ CD8+ T cells, significantly correlated with a clinical severity score. Altogether, our data, showing that CD4dimCD8+T cells are increased in patients with MAS/sHLH and associated with disease severity, strongly support their involvement in MAS/sHLH pathogenesis. |
Naturally Selected CD7 CAR-T Therapy without Genetic Manipulations for T-ALL/LBL: First-in-human Phase I Clinical Trial. These results indicate that NS7CAR-T therapy is a safe and highly effective treatment for T-ALL/T-LBL. More patients and longer follow-up are needed for validation. Clinical Trial can be found at NCT04572308, |
Thrombocytopenia and splenic platelet directed immune responses after intravenous ChAdOx1 nCov-19 administration. This is followed by a pronounced B-cell response with the emergence of circulating antibodies binding to platelets. Our work contributes to the understanding of platelet associated complications after ChAdOx1 nCov-19 administration and highlights accidental intravenous injection as a potential mechanism of platelet targeted autoimmunity. Hence, preventing intravenous injection when administering adenovirus-based vaccines could be a potential measure against platelet associated pathologies following the vaccination. |
Two SERPINC1 variants affecting N-glycosylation of Asn224 cause severe thrombophilia not detected by functional assays. Mutation experiments reflected the role that Lysine residues close to the N-glycosylation sequon have in impairing the efficacy of N-glycosylation. Our study shows new elements involved in the regulation of N-glycosylation, a key post-translational modification that, according to our results affects folding, secretion and function, providing new evidence of the pathogenic consequence of an incorrect N-glycosylation of antithrombin. This study supports that antithrombin deficiency is underestimated and encourages the development of new functional and genetic tests to diagnose this severe thrombophilia. |
| Blood Adv |
Alterations in B- and circulating T-follicular helper cell subsets in immune thrombotic thrombocytopenic purpura. The subsequent kinetics of naïve, transitional, memory B cells and plasmablasts did not differ significantly between patients who went on to relapse vs those who remained in remission. In summary, acute iTTP is characterised by dysregulation of B- and cTfh-cell homeostasis with depletion of post-GC memory cells and cTfh cells and increased plasmablasts. Changes in CD80 expression on B cells further suggest altered interactions with T cells. |
CD22low/Bcl-2high expression identifies poor response to inotuzumab in relapsed/refractory acute lymphoblastic leukemia. Our analyses identified frequencies of CD22high cells and CD22low/Bcl-2high cells as predictors of good and poor response, respectively. Furthermore, residual blasts at end of cycle 1 or 2 showed persistently high expression of Bcl-2 family members. These data provide new insights into predictors of InO treatment and raise the potential of Bcl-2 family inhibitors as concurrent therapy in these patients. |
CD44-fibrinogen binding promotes bleeding in acute promyelocytic leukemia by in situ fibrin(ogen) deposition. In vivo studies revealed that CD44 knockdown shortened bleeding time, increased the level of fibrinogen, and elevated the number of platelets by approximately 2-fold in an APL mouse model. Moreover, CD44 expression on leukaemic cells in an APL mouse model was not only associated with bleeding complications but was also related to the wound healing process and the survival time of APL mice. Collectively, our results suggest that CD44 may be a potential intervention target for preventing bleeding complications in APL. |
Evaluation of allogeneic and autologous membrane-bound IL-21-expanded NK cells for chronic lymphocytic leukemia therapy. As any CLL immune therapy would likely be given in combination, we assess commonly-used treatments and demonstrate that ibrutinib has mixed suppressive and protective effects on expanded NK cells whereas expanded NKs are highly resistant to venetoclax. We demonstrate efficacy in vivo in two xenograft mouse models of human CLL that support building upon a regimen of venetoclax and obinutuzumab with mbIL-21-expanded NK cells. Collectively, these data support development of mbIL-21-expanded NKs combined with the CD20 antibody obinutuzumab and venetoclax in the treatment of CLL. |
IFN Whereas chemical or genetic disruption of mitochondrial complex I (rotenone treatment or Leigh Syndrome patient monocytes) or NADPH oxidase (DPI treatment or chronic granulomatous disease (CGD) patient monocytes) reduced OCR. Interestingly, inhibition of NAMPT in healthy monocytes completely abrogated the IFN |
Influence of N-glycosylation in the A and C domains on the immunogenicity of factor VIII. The reduction of inhibitor response by N2118Q FVIII variant was also demonstrated in AAV-mediated gene transfer experiments. Furthermore, a specific glycopeptide epitope surrounding the N2118 glycosylation site was identified and characterized to activate T cells in a FVIII-specific proliferation assay. These results indicate that N-glycosylation of FVIII can have significant impact on its immunogenicity. |
Interaction between maternal killer immunoglobulin-like receptors and offspring HLAs and susceptibility of childhood ALL. Among non-Latino White subjects, no significant association was observed between offspring HLA-maternal KIR interaction and ALL risk, or cytokine levels. The current study reports the association between offspring HLA-maternal KIR interaction and the development of childhood ALL with variation by predicted genetic ancestry. We also observed some associations between activating profiles and immune factors related to cytokine control; however, cytokines did not demonstrate causal mediation of the activating profiles on ALL risk. |
Metformin for Treatment of Cytopenias in Children and Young Adults with Fanconi Anemia. Plasma proteomics showed reduction in inflammatory pathways with metformin. We conclude that metformin is safe and tolerable in non-diabetic patients with FA and may provide therapeutic benefit. This trial is registered at as NCT03398824. |
Midostaurin plus intensive chemotherapy for younger and older Patients with AML and FLT3 internal tandem duplications. The treatment effect of midostaurin remained significant in sensitivity analysis including allogeneic HCT as a time-dependent covariate. Addition of midostaurin to chemotherapy was safe in younger and older patients. In comparison to historical controls, the addition of midostaurin to intensive therapy led to a significant improvement in outcome in younger and older patients with AML and FLT3-ITD. |
Overlapping and unique substrate specificities of ST3GAL1 and 2 during hematopoietic and megakaryocytic differentiation. In contrast, O-sialylation of GPIIb relied predominantly on the expression of ST3GAL2. Finally, while disruption of ST3GAL1 and ST3GAL2 had little impact on MK production, their absence resulted in dramatically impaired MK proplatelet formation. Taken together, these data establish heretofore unknown physiological roles for ST3GAL1 and ST3GAL2 in O-linked glycan sialylation in hemato- and megakaryocyto-poiesis. |
Racial and ethnic differences in clonal hematopoiesis, tumor markers, and outcomes of patients with multiple myeloma. Differences in tumor expression of BCL7A, SPEF2, and ANKRD26 were observed by race and ethnicity. Clonal hematopoiesis was observed in 12% of patients and associated with inferior OS in non-Hispanic Black patients compared to patients without clonal hematopoiesis (HR 4.36, 95% CI 1.36-14.00), although this association was attenuated after adjusting for prognostic factors. This study provides insight into differences in molecular features that may drive clinical disparities in MM patients receiving comparable treatment, with the novel inclusion of Hispanic individuals. |
Real-world effectiveness of CPX-351 vs venetoclax and azacitidine in acute myeloid leukemia. Hospital length of stay, including any admission prior to next cycle of therapy, was more than twice as long for CPX-351. In this large multi-center real word dataset, there was no statistically significant difference in OS. Prospective randomized studies with careful attention to side effects, quality of life, and impact on transplant outcomes are needed in these populations. |
Single-cell transcriptomics reveals the identity and regulators of human mast cell progenitors. Culture assays showed that interleukin-3 (IL-3) and IL-5 promoted disparate effects on progenitor cell proliferation and survival, respectively, whereas IL-33 caused robust FceRI downregulation. Taken together, we have revealed that FceRI expression appears at the progenitor stage of mast cell differentiation in peripheral blood. We also demonstrated that external stimuli regulate the FceRI expression of mast cell progenitors, providing a possible explanation for the variable FceRI expression levels during mast cell development. |
Treatment-free remission after ceasing venetoclax-based therapy in patients with acute myeloid leukemia. With follow up exceeding 5 years, we observed a median TFR lasting 45.8 months among the STOP cohort, with >50% of patients still in sustained remission at the data cut-off. The risk of relapse and duration of relapse-free and overall survival were similar between the two cohorts. Factors favoring sustained TFR within the cohort included NPM1 and/or IDH2 mutation at diagnosis, complete remission without measurable residual disease, and at least 12 months of VEN-based combination therapy prior to treatment cessation. |
| Blood Cancer J |
Hypomethylating agent and venetoclax with FLT3 inhibitor "triplet" therapy in older/unfit patients with FLT3 mutated AML. Triplet therapy was associated with significantly higher rates of complete remission (CR) (67% versus 32%, P |
PET2 response associated with survival in newly diagnosed diffuse large B-cell lymphoma: results of two independent prospective cohorts. Revised response criteria 2007 were used to define PET2 response PET2 positive (PET2 |
| Haematologica |
Patient- and physician-reported pain after tyrosine kinase inhibitor discontinuation among patients with chronic myeloid leukemia. Three patients (1.7%) restarted a TKI because of pain. The modelpredicted trajectory showed an increase in pain in the first 3 months followed by a decrease, returning to baseline levels by 6 months and further decreasing after that. This trajectory was similar among patients who did and did not restart TKI, suggesting that resuming a TKI for withdrawal syndrome may be necessary for some, but other approaches to manage pain should be tried so that patients can remain in TFR when possible. |
Relapse of immune-mediated thrombotic thrombocytopenic purpura following mRNA COVID-19 vaccination: a prospective cohort study. Four of five cases had concomitant clinical relapse and were treated with corticosteroids alone or daily sessions of plasma exchange and caplacizumab, while one patient was closely monitored with ADAMTS13 with no onset of anemia and thrombocytopenia. Although the benefits of vaccination exceed its potential risks, clinicians should be aware that iTTP relapse might follow COVID-19 vaccination. Therefore, laboratory and clinical monitoring of iTTP patients should be done in the first post-vaccination month, in order to promptly diagnose and treat any relapse. |
| J Hematol Oncol |
Universal immunotherapeutic strategy for hepatocellular carcinoma with exosome vaccines that engage adaptive and innate immune responses. These findings demonstrate the capacity of universal DEX vaccines to induce tumor-specific immune responses by triggering an immune response tailored to the tumors of each individual, thus presenting a generalizable approach for personalized immunotherapy of HCC, by extension of other tumors, without the need to identify tumor antigens. |
| Leukemia |
Increased expression of RUNX3 inhibits normal human myeloid development. Overexpression of RUNX3 in the context of RUNX1::ETO did not rescue the RUNX1::ETO-mediated block in differentiation. RNA-sequencing showed that RUNX3 overexpression downregulates key developmental genes, such as KIT and RUNX1, while upregulating lymphoid genes, such as KLRB1 and TBX21. Overall, these data show that increased RUNX3 expression observed in AML could contribute to the developmental arrest characteristic of this disease, possibly by driving a competing transcriptional program favoring a lymphoid fate. |
MiRNA-363-3p/DUSP10/JNK axis mediates chemoresistance by enhancing DNA damage repair in diffuse large B-cell lymphoma. Ectopic expression of miRNA-363-3p more effectively repaired doxorubicin-induced double-strand break (DSB) while enhancing non-homologous end joining repair and reducing HR repair. Targeting JNK and poly (ADP-ribose) polymerase 1 significantly inhibited doxorubicin-induced DSB repair, increased doxorubicin-induced cell apoptosis and tumor shrinkage, and improved the survival of tumor-bearing mice. In conclusion, the miRNA-363-3p/DUSP10/JNK axis is a novel chemoresistance mechanism in DLBCL that may be reversed by targeted therapy. |
RUNX1 mutations contribute to the progression of MDS due to disruption of antitumor cellular defense: a study on patients with lower-risk MDS. Dysregulated DDR and cellular senescence were also observed at the functional level by detecting |
Plenty of the editorials are available as full text through the publisher website using the provided link
| Am J Hematol |
Unusual complications in the management of CLL. CLL may also infiltrate extranodal sites in the body. Symptomatic extranodal CLL or extranodal disease which threatens normal organ function is an indication for initiation of CLL directed therapy. The following review summarizes autoimmune and extranodal complications that can occur in patients with CLL and our suggested approach to their treatment. |
| Blood |
| J Hematol Oncol |
3D chromatin architecture and transcription regulation in cancer. In turn, aberrant 3D structures play a vital role in developing abnormalities and diseases such as cancer. This review discusses key 3D chromatin structures (topologically associating domain, lamina-associated domain, and enhancer-promoter interactions) and corresponding structural protein elements mediating 3D chromatin interactions [CCCTC-binding factor, polycomb group protein, cohesin, and Brother of the Regulator of Imprinted Sites (BORIS) protein] with a highlight of their associations with cancer. We also summarise the recent development of technologies and bioinformatics approaches to study the 3D chromatin interactions in gene expression regulation, including crosslinking and proximity ligation methods in the bulk cell population (ChIA-PET and HiChIP) or single-molecule resolution (ChIA-drop), and methods other than proximity ligation, such as GAM, SPRITE, and super-resolution microscopy techniques. |
Gut microbiota influence immunotherapy responses: mechanisms and therapeutic strategies. Deciphering the underlying mechanisms reveals that the gut microbiota reprogram the immunity of the tumor microenvironment (TME) by engaging innate and/or adaptive immune cells. Notably, one of the primary modes by which the gut microbiota modulate antitumor immunity is by means of metabolites, which are small molecules that could spread from their initial location of the gut and impact local and systemic antitumor immune response to promote ICI efficiency. Mechanistic exploration provides novel insights for developing rational microbiota-based therapeutic strategies by manipulating gut microbiota, such as fecal microbiota transplantation (FMT), probiotics, engineered microbiomes, and specific microbial metabolites, to augment the efficacy of ICI and advance the age utilization of microbiota precision medicine. |
| Lancet Haematol |
The case for classical haematology: the impact of a name and the future of a field. In this Viewpoint, we argue that use of the terms benign and non-malignant to describe this field dismisses patient suffering, dampens trainee interest, and diminishes the field as a whole. We propose more uniform adoption of the term classical haematology by organisations, academic divisions, and clinical practices, as this term avoids the conscious and unconscious devaluation of the "benign" and "non-malignant" descriptors. Unlike the alternatives, the term classical haematology evokes the field's rich, centuries-long history of numerous scientific advances central to every aspect of medicine, including discoveries by women and people of colour, thereby fostering interest and recruitment among trainees and dignifying patients living with serious non-cancerous haematological diseases. |
| Leukemia |
Recommendations for the management of COVID-19 in patients with haematological malignancies or haematopoietic cell transplantation, from the 2021 European Conference on Infections in Leukaemia (ECIL 9). Moreover, the recent emergence of new variants may require vaccine modifications and strategies to improve efficacy in these vulnerable patients. Beyond supportive care, the specific treatment is directed at viral replication control (antivirals, anti-spike monoclonal antibodies) and, in patients who need it, to the control of inflammation (dexamethasone, anti-Il-6 agents, and others). However, the benefit of al these various prophylactic and therapeutic treatments in haematology patients deserves further studies. |
Letters to the editors and authors’ replies
| Ann Oncol |
| J Hematol Oncol |
Prostate cancer multiparametric magnetic resonance imaging visibility is a tumor-intrinsic phenomena. e., International Society of Urological Pathology (ISUP) Grade Group 2)-twenty mpMRI-visible and twenty mpMRI-invisible, with matched histologically normal prostate. Normal prostate tissue was indistinguishable between patients with visible and invisible tumors, and invisible tumors closely resembled the normal prostate. These data indicate that mpMRI-visibility arises when tumor evolution leads to large-magnitude proteomic divergences from histologically normal prostate. |
all remaining publications eg case reports, images of the month, etc…
| Blood |
| Blood Adv |
| Haematologica |
| Lancet Haematol |
| Leukemia |